Aromatic Hydroxylation of Estrogens

The metabolism of an endogenous steroid hormone has traditionally been viewed as a means of terminating its activity and facilitating its excretion. In recent years, however, examples have accumulated (18,50,76) in which such biotransformations have been shown to have activating rather than inactivating functions, placing the role of metabolism in the expression of hormonal action into a new context. The mammalian metabolism of the female sex hormone is almost exclusively oxidative in nature and is domi­ nated by three pathways, of which the largest and fastest is the oxidation of the 17 ,B-hydroxy function to the 17 ketone (23). This process in revers­ ible, but the equilibrium greatly favors the oxidized estrone form, which is the principal substrate for the other two main oxidative transformations, hydroxylation at the C-2 or C-16a positions of the molecule. The 16a-hydroxylative pathway, whose most noted product is estriol, was rec­ ognized early (59), but the hydroxylation at the C-2 position of the aromatic ring has been detected only relatively recently (52). This biotransformation of estrogens and the even more recently discovered hydroxylation at the isomeric C-4 position (83) have attracted much interest and have generated a substantial literature. The nature of these transformations and the biologi­ cal properties of their polyphenolic products, the catechol estrogens, are reviewed in this chapter. This review is selective. The reader seeking more detailed information is directed to an exhaustive survey of the field (6), which covers the available information through 1979.